2023
DOI: 10.1038/s41467-023-43134-0
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A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics

Hyeong-Min Lee,
William C. Wright,
Min Pan
et al.

Abstract: Combination chemotherapy is crucial for successfully treating cancer. However, the enormous number of possible drug combinations means discovering safe and effective combinations remains a significant challenge. To improve this process, we conduct large-scale targeted CRISPR knockout screens in drug-treated cells, creating a genetic map of druggable genes that sensitize cells to commonly used chemotherapeutics. We prioritize neuroblastoma, the most common extracranial pediatric solid tumor, where ~50% of high-… Show more

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Cited by 5 publications
(2 citation statements)
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“…S2), raises the question as to the degree to which cell line specificity may be a broader attribute of paralogue-specific EP300 degraders. For example, JQAD-1’s mechanism was recently validated in a study showing that CRBN KO confers resistance in several models, 30 but this was observed in only 9/19 cell lines tested. MC-1’s ability to inhibit H3K18Ac in MCF-7 would argue against differential occupancy being the sole determinant of this variability.…”
mentioning
confidence: 99%
“…S2), raises the question as to the degree to which cell line specificity may be a broader attribute of paralogue-specific EP300 degraders. For example, JQAD-1’s mechanism was recently validated in a study showing that CRBN KO confers resistance in several models, 30 but this was observed in only 9/19 cell lines tested. MC-1’s ability to inhibit H3K18Ac in MCF-7 would argue against differential occupancy being the sole determinant of this variability.…”
mentioning
confidence: 99%
“…This, along with the observation that JQAD-1 was inactive in HAP-1 cells (Figure S2), raises the question as to the degree to which cell line specificity may be a broader attribute of paralogue-specific EP300 degraders. For example, JQAD-1's mechanism was recently validated in a study showing that CRBN KO confers resistance in several models, 32 but this was observed in only 9/ 19 cell lines tested. MC-1's ability to inhibit H3K18Ac in MCF-7 would argue against differential occupancy being the sole determinant of this variability.…”
mentioning
confidence: 99%